The present invention relates generally to antimicrobial laminates, such as surgical drapes, employing chlorhexidine.
Many types of surgical drapes are known. Some include an adhesive layer for adhering the surgical drape to a patient's skin or other surface. One such drape is an incise drape. An “incise drape” is one where a surgical incision is made directly through the drape and into a patient. By definition, a skin surface covered by a sterile incise drape is bacteria-free (i.e., sterilized) at the beginning of a surgical procedure. Ideally, the skin surface remains bacteria-free during the procedure, resisting the transfer of bacteria from, for example, gloves, instruments, and sponges that may come in contact with not only the surgical wound but also the surrounding skin. A drape's barrier and antimicrobial properties are typically effective only so long as the drape is securely attached to the skin.
Adhesion of a drape to skin can be affected by a wide variety of considerations, including the type of any skin prepping solution applied to the skin before the drape is adhered thereto. For example, a 2007 technical brochure published by 3M Company (St. Paul, Minn.) describes test results illustrating that 3M's DuraPrep Surgical Solution (an iodine povacrylex and isopropyl alcohol solution available from 3M Company of St. Paul, Minn.) facilitates better adhesion of drapes to skin prepped therewith as compared to skin prepped with ChloraPrep (a solution containing 2% chlorhexidine gluconate in 70% isopropyl alcohol available from Cardinal Health, Inc. through its Enturia Division in Leawood, Kans.).
In contrast to surfaces covered by a sterile incise drape, a skin surface that has been “prepped” has only been disinfected, not sterilized. It is known that prepping a skin surface does not always completely eradicate bacteria. Even after prepping, bacteria regeneration continuously occurs on a skin surface. Further, skin prepping solutions are vulnerable to removal or neutralization by blood, irrigation fluids, exudates, and the like, which are commonly associated with surgical procedures.
A variety of surgical incise drapes are known, but adequate adhesion of such drapes to skin is of ongoing concern. Conventional surgical incise drapes contain at least one skin-compatible adhesive coated on a backing. While many different chemistries have been contemplated for use in backings within surgical incise drapes, geometry of those backings is generally more limited. Conventional surgical drape backings are generally at least 1.5 mils (40 microns) thick. Such backings are conventionally used to impart, among other properties, structural integrity to the drape.
While the use of thinner backings is contemplated in certain configurations, those configurations are limited and specific. For example, U.S. Pat. No. 5,803,086 describes a film backing for surgical incise drapes as generally having a thickness of less than 200 microns (7.87 mils) and preferably about 6 to 130 microns (0.24 mil to 5.12 mils). The drapes therein are linerless.
Further, U.S. Pat. No. 5,183,664 describes a configuration where a hydrophilic polyurethane gel adhesive layer is interfaced with a backing. The adhesive layer may contain an antibacterial agent, including chlorhexidine and salts thereof. A backing layer having a thickness of as low as 10 microns (0.39 mil) is described in this configuration. In such a configuration, however, the backing does not provide structural integrity, but merely functions as an outwardly exposed barrier layer. The adhesive layer has a thickness of 10 microns (0.39 mil) to 100 microns (3.94 mils), preferably 35 microns (1.38 mils) to 45 microns (1.77 mils), when used in conjunction with nonexuding wounds. However, the adhesive layer is stated to have a thickness of 0.5 mm (19.69 mils) to 5 mm (196.85 mils), preferably 2 mm (78.74 mils) to 3 mm (118.11 mils), when used in conjunction with exuding wounds. The use of substantially thicker adhesive layers as compared to those traditionally used in incise drapes and dressings is described as being driven by the desire to take advantage of the absorptive properties of the material forming the adhesive layer. Generally, however, the thicker the backing and other layer(s) of materials within a surgical incise drape, the more difficult it tends to be for such drapes to conform to a patient's skin surface and stay adequately adhered to that skin surface. For example, when performing an incision through such a drape, force from frictional drag of a scalpel used to make such an incision can cause lifting of the incise drape's edge during use. Further, when drapes are used to cover areas on a patient's skin that undergo significant movement during the surgical procedure (e.g., when drapes are placed proximate a knee joint being replaced, during which procedure the replacement knee joint must be extensively manipulated after its implant to ensure proper range of motion and fit), lifting of the incise drape from the skin surface is more likely.
Adding to the challenge of adequate adherence of a surgical incise drape to skin is compatibility of the adhesive with not only the skin but also any antimicrobial agents incorporated therein. Select antimicrobial agents have been incorporated into skin-compatible adhesives.
For example, U.S. Pat. No. 4,323,557, assigned on its face to 3M Company, describes a pressure-sensitive adhesive containing iodine. 3M Company markets an iodine-containing surgical drape under the IOBAN trade designation. 3M IOBAN 2 Antimicrobial Incise Drapes, available from 3M Company of St. Paul, Minn., are stated to be useful in reducing the risk of wound contamination and bacterial migration. 3M IOBAN 2 Antimicrobial Incise Drapes—6661 EZ, also available from 3M Company of St. Paul, Minn., are stated to be specifically adapted for minimally invasive surgical procedures using implantable devices and/or materials. According to 3M Company's technical literature, an iodophor-impregnated adhesive on such incise drapes is stated to provide continuous, broad-spectrum antimicrobial activity and superior adhesion to the skin and wound edge. See also U.S. Pat. No. 7,189,793, assigned on its face to 3M Innovative Properties Company, which discloses an iodine/iodide-containing hot melt coatable adhesive used in surgical drapes.
Iodine, however, has not proven to be as effective as desired in halting the spread of bacteria promoting staphylococcal infections. Staphylococcal (i.e., “staph”) infections are communicable infections caused by staph organisms, and they are often characterized by the formation of abscesses. They are said to be the leading cause of primary infections originating in hospitals in the United States.
Classified since the early twentieth century as among the deadliest of all disease-causing organisms, staph exists on the skin or inside the nostrils of 20-30% of healthy people. It is sometimes found in breast tissue, the mouth, and the genital, urinary, and upper respiratory tracts. Although staph bacteria are usually harmless, when injury or a break in the skin enables the organisms to invade the body and overcome the body's natural defenses, consequences can range from minor discomfort to death. Infection is most apt to occur in the following classes of people: newborns (especially those born prematurely); women who are breast-feeding; individuals whose immune systems have been undermined by radiation treatments, chemotherapy, HIV, or medication; intravenous drug users; and those with surgical incisions, skin disorders, and serious illnesses like cancer, diabetes, and lung disease. Risk of infection is greatest among the very young and the very old.
The United States' Center for Disease Control (CDC) recommends chlorhexidine gluconate as the preferred skin antiseptic over tinctures of iodine, iodophors, and alcohol. Chlorhexidine gluconate, however, is a cationic molecule that is known to become inactive over time if exposed to anionic materials on, for example, skin. Nevertheless, chlorhexidine gluconate has been recently introduced by 3M Company (St. Paul, Minn.) into dressings used, for example, in dressing catheter insertion sites. 3M Company's TEGADERM CHG (Chlorhexidine Gluconate) IV Securement Dressing is stated to provide the antimicrobial properties of chlorhexidine gluconate with the simplicity, reliability, and dependability of 3M's TEGADERM dressings. In order to extend the typically short antimicrobial life of chlorhexidine gluconate within the dressing, 3M Company's technical literature describes how the chlorhexidine gluconate is dissolved into a soft gel pad to provide a reservoir of antiseptic for consistent and continuous coverage over time. The same latex-free adhesive is used to secure 3M Company's TEGADERM CHG IV Securement Dressing to skin as is used in 3M Company's non-CHG TEGADERM dressing. See also U.S. Pat. No. 6,461,467, assigned on its face to 3M Innovative Properties Company, which describes the use of an antimicrobial adhesive containing chlorhexidine gluconate with 3M Company's TEGADERM dressings.
Chlorhexidine, a substituted diguanide, has a high degree of antimicrobial activity, low mammalian toxicity, and the ability to bind to the stratum corneum layer of skin and to mucous membranes. The bactericidal activity of chlorhexidine is much greater than that of monomeric biguanides. These unique characteristics make it particularly attractive as an active ingredient in antimicrobial skin preparations.
Besides its use in specific medical dressings and skin antiseptics, the efficacy of chlorhexidine in providing antimicrobial protection is known further throughout the medical industry. For example, U.S. Pat. No. 7,329,412 describes an antimicrobial catheter prepared by treating a polymeric catheter with a solution comprising a solvent and an antimicrobial mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt, wherein the weight ratio of chlorhexidine free base to water-soluble chlorhexidine salt in the solution is between 1:1 to 1:5. As background therein, duration of the antimicrobial efficacy of medical devices impregnated with chlorhexidine salts, such as chlorhexidine acetate, is discussed as being short lived. Further discussed is the fact that chlorhexidine free base is not generally known to be soluble in water or alcohol, which generally prevents it from being impregnated in sufficient amounts because of low solubility in a solvent system. Thus, the combination of chlorhexidine free base and a water-soluble chlorhexidine salt, at the particular ratios described therein, was found to provide improved antimicrobial effectiveness through an increased uptake of chlorhexidine into, increased retention of chlorhexidine in, and prolonged release of chlorhexidine from the medical device, while utilizing relatively low levels of chlorhexidine.
U.S. Pat. No. 5,165,952 relates to medical articles employing chlorhexidine. When bulk-distributed in a medical article, chlorhexidine is described as being known to adversely affect certain characteristics of the article, such as tensile strength; and, when the medical article is formed of a plastic material, high temperatures often needed for extension of such plastic materials into the form of a medical article are described as potentially damaging the chlorhexidine within. Thus, chlorhexidine is both coated on and bulk-distributed throughout the medical articles according to the disclosure therein. Similarly, U.S. Pat. No. 5,089,205 relates to incorporation of chlorhexidine free base or one of its salts into a medical device such as a glove. The chlorhexidine can be incorporated by both distribution and dipping processes.
Chlorhexidine, in its pure form and in its salt forms, is also discussed as being useful as a preservative and as an antimicrobial in compositions for oral hygiene. See, for example, U.S. Patent Publication No. 20050158252.
U.S. Patent Publication No. 20080026025 also discusses the use of chlorhexidine, specifically in water purification applications. As discussed therein, chlorhexidine is a 1,6-di(4-chlorophenyl-diguanido) hexane having the chemical formula:
Chlorhexidine is discussed therein as having a high level of antibacterial activity, low mammalian toxicity, and a strong affinity for binding to skin and mucous membranes.
Also discussed in U.S. Patent Publication No. 20080026025 is the history of using chlorhexidine only in its salt soluble forms. Chlorhexidine salts are stated to have an extremely bitter taste that must be masked in formulations intended for oral use. In addition, chlorhexidine salts are stated to be ineffective for applications requiring insoluble materials. As such, preparation and use of chlorhexidine dihydrate in accordance with the disclosure therein was found to provide advantages over known chlorhexidine-containing compositions.
Chlorhexidine dihydrate is described in U.S. Patent Publication No. 20080026025 as being amorphous in structure as opposed to the 100% crystalline structure of pure chlorhexidine. Chlorhexidine dihydrate is also described as disrupting microorganisms in a principally surface-dependent manner, advantageously without depleting the supply of the chlorhexidine dehydrate (i.e., the antimicrobial functionality is effectively catalytic). Such treatment, being a zero-order reaction, was found capable of proceeding without consumption of any chlorhexidine dihydrate. In contrast, the rate of reaction for pure chlorhexidine and its previously known conventional derivatives is described therein as being second-order, as those reactions depend on both the concentration of chlorhexidine and the active sites of microorganisms. In such conventional reactions, chlorhexidine is described as being consumed during the reaction.
Nevertheless, improved antimicrobial laminates, such as surgical drapes, are desired. For example, improvements with respect to a surgical drape's or other medical dressing's adhesion to a variety of skin surfaces and its role in halting the spread of bacteria promoting staphylococcal infections are needed.